HCV very late relapse following an atypical viral kinetics in a HIV patient treated for hepatitis C with direct-acting antivirals

Direct-acting antivirals (DAAs) for the treatment of HCV have dramatically increased the rate of sustained virological response: patients not achieving sustained virological response represent a challenge and rates of late recurrent viremia are very low. We describe here the first case of a very late HCV relapse, following an atypical kinetics (characterized by a spontaneous but transient HCV clearance after an early virological relapse), in a HIV co-infected patient treated with DAAs. Optimal adherence to the therapy was well documented and a phylogenetic analysis ruled out a possible reinfection from a different HCV strain. In conclusion, our case underlines the importance of a long follow-up (>?48 weeks) after DAAs therapies in HCV–HIV co-infected patients who might benefit the most from a very rigorous virological surveillance.     

Feeding during acute diarrhea as a risk factor for persistent diarrhea

Dietary intake during diarrhea in children less than three years of age was estimated from information recorded on illustrated dietary forms used by children's caretakers during the first week of illness in a prospective community-based study of diarrheal diseases in Lima, Peru. The frequency of consumption and the amount consumed of food groups and selected commonly consumed foods were analyzed by the final duration of the diarrheal episode. Cereals were less frequently consumed during the acute phase of diarrheal episodes that ultimately became persistent (>14 days'duration), apparently shortening the duration of the episode by one day (median duration of four days in children not consuming vs three days in children consuming cereals during diarrhea, p <0.02 Kaplan-Meier logrank test). Only roots and tubers (mainly potatoes) were consumed in greater quantity during episodes that became persistent. There was no evidence that consumption of breast milk or non-maternal milk was associated with an alteration in diarrheal duration. This study provides further evidence of the beneficial effects of continuing feeding during diarrhea using foods available at the home level, especially cereals, which are commonly used in the diet of young children.     

Arterial oxygen saturation in infants at risk of sudden death: influence of sleeping position

To study the possible influence of sleeping position on arterial oxygen saturation, measured by pulse oximetry (Sp6₂), 7–h overnight recordings of breathing movements and ECG were performed in 43 infants (median age 2.4 months, range 0.2–11 months) at increased risk of sudden infant death syndrome (SIDS). Infants were randomly allocated to start sleeping either in their usual sleeping position or in the opposite position. After 3.5 h, all infants were gently turned over. Thus, each infant served as their own control. Recordings were analysed for sleep time, baseline Sp0₂ (only during regular breathing), and the number and duration of desaturations (a decrease in Sp0₂ to ≤80%). In the prone position, a significantly higher proportion of time was spent asleep (median 79% versus 70%; p < 0.05). Median baseline Sp0₂ was 98.8% (91.7–100%) in the prone and 99.0% (92.0–100%) in the supine position (ns). A total of 191 desaturations were found in 29 recordings; 96 in the prone and 95 in the supine position (ns). One infant subsequently died of SIDS while sleeping in the prone position. He had a relatively high number of desaturations (n = 12) which all occurred in the prone position. These results confirm earlier studies which could not find a significant influence of sleeping position on baseline oxygenation. The occurrence of desaturations in the prone position only in the infant who subsequently died requires further investigation.     

Use of E mu-PIM-1 transgenic mice short-term in vivo carcinogenicity testing: lymphoma induction by benzo[a]pyrene, but not by TPA

E mu-pim-1 transgenic mice are predisposed to develop lymphomas. Due to their low spontaneous tumour incidence and their increased sensitivity towards the lymphomagen ethylnitrosourea these mice may present an interesting model for short-term carcinogenicity testing. Here, we report on the further exploration of this transgenic mouse model with two additional carcinogens known to have, among others, the lymphohaematopoietic system as target, i.e. benzo[a]pyrene (B[a]P) and 12-O-tetradecanoylphorbol-13-acetate (TPA). B[a]P, given three times a week (by gavage) for 13 weeks at 4.3, 13 or 39 mg/kg body weight, resulted in a dose-related increase in lymphomas up to a 90% incidence in E(mu)-pim-1 mice during the observation period of 40 weeks. B[a]P also induced tumours of the forestomach within this observation period, though at a lower incidence and apparently equally effective in wildtype and transgenic mice. TPA, on the other hand, was unable to induce lymphomas (or tumours in any other organ) in either transgenic or wildtype animals within the observation period of 44 weeks, when applied dermally at the maximum tolerated dose of 3 microg/mouse, twice a week for 35 weeks. Molecular analysis showed that B[a]P-induced lymphomas in transgenic mice were of T-cell origin, 80% of which had elevated levels of c-myc expression. None of the lymphomas had increased N-myc expression and mutation analysis of the ras-gene family revealed a K-ras mutation in only one out of eight tumours investigated. Also, none of the lymphomas showed aberrant expression of p53 as determined by immunohistochemistry. It is concluded that the E mu-pim-1 mouse model will not be very suitable for short-term carcinogenicity testing in general: only genotoxic chemicals that have the lymphohaematopoietic system as target for carcinogenesis in wild- type mice, appear to be efficiently identified.      

HIV infection in haemophilia--a European cohort

Ten haemophilia centres in northern Europe have pooled data on 202 haemophilic children who were infected with HIV between 1979 and 1986. All cases were under 16 years of age on 1 July 1985. The age at infection ranged from 1-15 years. Thirty seven cases (18%) had progressed to AIDS by 1 July 1991 and 15 of these have died. Persistent generalised lymphadenopathy has been noted in 102 patients of whom 18 (17%) have developed AIDS. Twenty three of the remaining patients (23%) have not. CD4+ T cell counts have fallen steadily. Of 36 patients who have had shingles since seroconversion, 19 (53%) had counts below 0.2 x 10(9)/l. Thirty five out of 145 patients without shingles (24%) had similar values. The mean IgA concentration in patients with CD4+ T cell counts above 0.5 x 10(9)/l was 2.38 g/l, between 0.2 and 0.5 was 3.07 g/l, and in those with CD4+ T cell counts below 0.2 x 10(9)/l the mean IgA concentration was 4.58 g/l. Treatment patterns have altered between 1989 and 1991, with increased use of zidovudine in patients without AIDS and a marked increase in primary prophylaxis against pneumocystis pneumonia. This has been associated with a decline in the incidence of pneumocystis as an indicator disease in new AIDS cases from 56% in 1989 to 20% in 1991. These observations indicate that persistent generalised lymphadenopathy does not worsen the outlook, but shingles does. Rising IgA concentrations are markers for disease progression. Modern prophylactic regimens are delaying the onset of indicator disease, but CD4 values continue to fall steadily.     

Macrophage depletion induced by clodronate-loaded erythrocytes

Given the important role of macrophages in various disorders, the transient and organ specific suppression of their functions may benefit some patients. Until now, liposome-encapsulated bisphosphonate clodronate has been extensively proposed to this end. In this paper, we demonstrate that erythrocytes loaded with clodronate can also be effective in macrophage depletion. Here, clodronate was encapsulated in erythrocytes through hypotonic dialysis, isotonic resealing and reannealing to final concentrations of 4.1 +/- 0.4 and 10.1 +/- 0.8 micromol/ml of human and murine erythrocytes, respectively. The ability of clodronate-loaded erythrocytes to deplete macrophages was evaluated both in vitro and in vivo. In vitro studies on human macrophages showed that a single administration of engineered erythrocytes was able to reduce cell adherence capacity in a time-dependent manner, reaching 50 +/- 4% reduction, 13 days post treatment. The administration of loaded erythrocytes to cultures of murine peritoneal macrophages was able to reduce macrophage adhesion 67 +/- 3%, 48 h post treatment. In vivo, the ability of clodronate-loaded erythrocytes to deplete macrophages was evaluated both in Swiss and C57BL/6 mice. Swiss mice received 125 microg of clodronate through erythrocytes and 6 days post treatment 69 +/- 7% reduction in the number of adherent peritoneal macrophages and 75 +/- 5% reduction in number of spleen macrophages were observed. C57BL/6 mice received 220 microg clodronate by RBC and 3 and 8 days post treatment 65 +/- 7% reduction in the number of spleen macrophages and the complete depletion of liver macrophages were obtained. In summary, our results indicate that clodronate selectively targeted to the phagocytic cells by a single administration of engineered erythrocytes is able to deplete macrophages, even if not completely. The transient suppression of macrophage functions through clodronate-loaded erythrocytes can be used in many biomedical phenomena and research applications.